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Gene Expression Profiling of Infecting Microbes Using a Digital Bar-coding Platform
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Host Gene Expression to Predict Sepsis Progression.

Cassandra Fiorino1, Yiling Liu1, Ricardo Henao1,2

  • 1Duke Center for Applied Genomics and Precision Medicine, Duke University School of Medicine, Durham, NC.

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|September 30, 2022
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Summary
This summary is machine-generated.

Host gene expression cannot reliably predict sepsis progression using the Sepsis-3 category. However, transcriptomic signatures showed potential for predicting ICU admission or death, though not with sufficient accuracy for clinical use.

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Area of Science:

  • Genomics
  • Computational Biology
  • Infectious Disease

Background:

  • Sepsis leads to significant mortality, often without clear signs of severe infection.
  • Host gene expression changes precede clinical manifestation of illness.
  • Early intervention is crucial but hampered by delayed diagnosis.

Purpose of the Study:

  • Develop transcriptomic models to predict sepsis or shock progression within 72 hours.
  • Validate existing transcriptomic signatures for predicting 28-day mortality.

Main Methods:

  • Retrospective analysis of RNA sequencing data from 277 patients with infection.
  • Utilized Least Absolute Shrinkage and Selection Operator (LASSO) modeling.
  • Evaluated four previously identified gene signatures for mortality prediction.

Main Results:

  • No significant gene expression differences were found when sepsis progression was defined by Sepsis-3 category increase.
  • 1,178 differentially expressed genes were identified when progression was defined by ICU admission or 28-day mortality.
  • A model based on these genes predicted progression (AUC 0.71); validated signatures predicted mortality (AUC 0.70-0.75).

Conclusions:

  • The Sepsis-3 category is not suitable for transcriptomic prediction of sepsis progression.
  • Transcriptomic signatures showed differential response for ICU admission or death prediction.
  • Existing signatures lack sufficient accuracy for clinical utility in predicting 28-day sepsis mortality.